I recently returned from the American College of Emergency Physicians (ACEP) Conference which took place from Oct. 26th – 29th, 2015 in Boston, MA. There were really a lot of amazing talks by so many amazing speakers but one lecture in particular by David Newman, of SMART EM and The NNT fame, made me realize that there is just so much research on treatment of ischemic stroke, that I can’t even keep them straight. So what I thought I would do is create an archive of all that research and continue to add to the list as more research is released. I don’t know about you, but I find myself spending lots of time looking this information up every time I need it.

Systemic Lytic Therapy in the Treatment of Ischemic Stroke

Trial

Lead Author

Year of Study

Patients

Outcome

MAST-I

Multicentre Acute Stroke Trial - Italy (MAST-I) Group

1995

622

No Benefit

ECASS-I

Hacke W

1995

620

No Benefit

NINDS-1

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group

1995

291

No Benefit

NINDS-2

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group

1995

333

12% Disability Benefit

MAST-E

Multicentre Acute Stroke Trial - Europe (MAST-E) Group

1996

310

Stopped Early due to Increased Death by 9%

ASK

Donnan GA

1996

340

Stopped Early due to Increased Death by 16%

ECASS-II

Hacke W

1998

308

No Benefit

ATLANTIS-B

Clark WM

1999

547

Stopped Early due to Increased Deaths by 14%

ATLANTIS-A

Clark WM

2000

142

Stopped Early due to Increased Deaths by 16%

ECASS-III

Hacke W

2008

821

8% Disability Benefit

DIAS-2

Hacke W

2009

186

Stopped Early due to Increased Deaths by 16%

IST-3

IST-3 Collaborative Group

2012

3035

No Benefit

DIAS-3

Albers GW

2012

492

No Benefit

What does the American College of Emergency Physicians (ACEP) 2015 Clinical Policy Say? [PDF HERE]

Is IV tPA safe and effective for patients with acute ischemic stroke if given within 3 hours of symptom onset?

Level A recommendations: None specified.

Level B recommendations: With a goal to improve functional outcomes, IV tPA should be offered and may be given to selected patients with acute ischemic stroke within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication. The increased risk of symptomatic intracerebral hemorrhage (sICH) should be considered when deciding whether to administer IV tPA to patients with acute ischemic stroke.

Level C recommendations: When feasible, shared decision making between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke (Consensus recommendation).

Is IV tPA safe and effective for patients with acute ischemic stroke treated between 3 to 4.5 hours after symptom onset?

Level A recommendations: None specified.

Level B recommendations: Despite the known risk of symptomatic intracerebral hemorrhage (sICH) and the variability in the degree of benefit in functional outcomes, IV tPA may be offered and may be given to carefully selected patients with acute ischemic stroke within 3 to 4.5 hours after symptom onset at institutions where systems are in place to safely administer the medication.

Level C recommendations: When feasible, shared decision making between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke (Consensus recommendation).

Disclaimer: This is by no means every piece of literature on the treatment of ischemic stroke, but instead a start to an archive that can continuously be updated. I was hoping the FOAM community might be willing to help out, to make this an even more robust evidence based archive that we can reference for future needs. Feel free to leave comments below, all help is welcome, and if there is literature not included feel free to put links in the comments as well. Appreciate everyone’s help and viva la FOAM!!!!

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Great post Salim, as usual.
Agree 100%:
1. Great idea to start with a reference list to refer to
2. Evidence for lysis is weak
3. Bottom line: one drug doesn’t fit all
4. We still don’t know the subgroups of patients who are likely to benefit from lysis (the carefully selected pts ACEP GL refer to)
5. More than 4.000 patients have been enrolled in lysis RCTs. The time for individual patient data metaanalysis has come?

Hello Roberto,
TY for reading and your comments. I agree, it would be nice to see a properly done systematic review/meta-analysis, but I have a feeling that the patient populations, lytic used, and outcomes may be a bit heterogenous. There was just a systematic review and meta-analysis on endovascular therapy for stroke, which I have in the reference list: Badhiwala JH et al. Endovascular Thrombectomy for Ischemic Stroke: A Meta-Analysis. JAMA 2015; 314(17): 1832 – 43. [epub ahead of print]. Hope all is well with you and always appreciate you reading and leaving comments/questions.